دورية أكاديمية
Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression.
| العنوان: | Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. |
|---|---|
| المؤلفون: | Alagpulinsa DA; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Cao JJL; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Pathology and School of Clinical Medicine, University of Cambridge, Cambridge, UK., Driscoll RK; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah., Sîrbulescu RF; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Penson MFE; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Sremac M; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Engquist EN; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts., Brauns TA; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Markmann JF; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Melton DA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts., Poznansky MC; Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. |
| المصدر: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2019 Jul; Vol. 19 (7), pp. 1930-1940. Date of Electronic Publication: 2019 Mar 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 100968638 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-6143 (Electronic) Linking ISSN: 16006135 NLM ISO Abbreviation: Am J Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Original Publication: Copenhagen : Munksgaard International Publishers, 2001- |
| مواضيع طبية MeSH: | Graft Survival*, Alginates/*chemistry , Chemokine CXCL12/*metabolism , Diabetes Mellitus, Experimental/*therapy , Diabetes Mellitus, Type 1/*therapy , Insulin-Secreting Cells/*cytology , Islets of Langerhans Transplantation/*methods , Stem Cells/*cytology, Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Experimental/immunology ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Female ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Stem Cells/metabolism |
| مستخلص: | Pancreatic β-cell replacement by islet transplantation for the treatment of type 1 diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, also referred to as SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement. Nonetheless, inflammatory foreign body responses leading to pericapsular fibrotic overgrowth often causes microencapsulated islet-cell death and graft failure. Here we used a novel approach to evade the pericapsular fibrotic response to alginate-microencapsulated SC-β cells; an immunomodulatory chemokine, CXCL12, was incorporated into clinical grade sodium alginate to microencapsulate SC-β cells. CXCL12 enhanced glucose-stimulated insulin secretion activity of SC-β cells and induced expression of genes associated with β-cell function in vitro. SC-β cells co-encapsulated with CXCL12 showed enhanced insulin secretion in diabetic mice and accelerated the normalization of hyperglycemia. Additionally, SC-β cells co-encapsulated with CXCL12 evaded the pericapsular fibrotic response, resulting in long-term functional competence and glycemic correction (>150 days) without systemic immunosuppression in immunocompetent C57BL/6 mice. These findings lay the groundwork for further preclinical translation of this approach into large animal models of T1D. (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.) |
| فهرسة مساهمة: | Keywords: basic (laboratory) research/science; diabetes: type 1; endocrinology/diabetology; fibrosis; immune regulation; immunosuppression/immune modulation; insulin/C-peptide; islet transplantation; islets of Langerhans; translational research/science |
| المشرفين على المادة: | 0 (Alginates) 0 (Blood Glucose) 0 (Chemokine CXCL12) 0 (Insulin) |
| تواريخ الأحداث: | Date Created: 20190213 Date Completed: 20200804 Latest Revision: 20230124 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1111/ajt.15308 |
| PMID: | 30748094 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1600-6143 |
|---|---|
| DOI: | 10.1111/ajt.15308 |